{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:51:58Z","timestamp":1773708718064,"version":"3.50.1"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2001,4,1]],"date-time":"2001-04-01T00:00:00Z","timestamp":986083200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Genet"],"published-print":{"date-parts":[[2001,4]]},"DOI":"10.1038\/86871","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T08:41:29Z","timestamp":1027672889000},"page":"375-382","source":"Crossref","is-referenced-by-count":376,"title":["Hepatocyte nuclear factor-1\u03b1 is an essential regulator of bile acid and plasma cholesterol metabolism"],"prefix":"10.1038","volume":"27","author":[{"given":"David Q.","family":"Shih","sequence":"first","affiliation":[]},{"given":"Markus","family":"Bussen","sequence":"additional","affiliation":[]},{"given":"Ephraim","family":"Sehayek","sequence":"additional","affiliation":[]},{"given":"Meenakshisundaram","family":"Ananthanarayanan","sequence":"additional","affiliation":[]},{"given":"Benjamin L.","family":"Shneider","sequence":"additional","affiliation":[]},{"given":"Frederick J.","family":"Suchy","sequence":"additional","affiliation":[]},{"given":"Sarah","family":"Shefer","sequence":"additional","affiliation":[]},{"given":"Jaya S.","family":"Bollileni","sequence":"additional","affiliation":[]},{"given":"Frank J.","family":"Gonzalez","sequence":"additional","affiliation":[]},{"given":"Jan L.","family":"Breslow","sequence":"additional","affiliation":[]},{"given":"Markus","family":"Stoffel","sequence":"additional","affiliation":[]}],"member":"297","reference":[{"key":"BFng0401_375_CR1","first-page":"155","volume-title":"Liver Gene Expression","author":"T Tranche","year":"1994","unstructured":"Tranche, T. et al. Hepatocyte nuclear factor-1 (HNF1) and liver gene expression. in Liver Gene Expression (eds. Tronche, F. & Yaniv, M.) 155\u2013181 (R.G. Landes, Austin, 1994)."},{"key":"BFng0401_375_CR2","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/384455a0","volume":"384","author":"K Yamagata","year":"1996","unstructured":"Yamagata, K. et al. Mutations in the hepatocyte nuclear factor-1\u03b1 gene in maturity-onset diabetes of the young. Nature 384, 455\u2013458 (1996).","journal-title":"Nature"},{"key":"BFng0401_375_CR3","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/S0092-8674(00)81033-8","volume":"84","author":"M Pontoglio","year":"1996","unstructured":"Pontoglio, M. et al. Hepatocyte nuclear factor 1 inactivation results in hepatic dysfunction, phenylketonuria, and renal Fanconi syndrome. Cell 84, 575\u2013585 (1996).","journal-title":"Cell"},{"key":"BFng0401_375_CR4","doi-asserted-by":"publisher","first-page":"3059","DOI":"10.1128\/MCB.18.5.3059","volume":"18","author":"YH Lee","year":"1998","unstructured":"Lee, Y.H., Sauer, B. & Gonzalez, F.J. Laron dwarfism and non-insulin-dependent diabetes mellitus in the Hnf-1\u03b1 knockout mouse. Mol. Cell. Biol. 18, 3059\u20133068 (1998).","journal-title":"Mol. Cell. Biol."},{"key":"BFng0401_375_CR5","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/S0092-8674(00)80213-5","volume":"89","author":"MS Brown","year":"1997","unstructured":"Brown, M.S. & Goldstein, J.L. The SREBP pathway: regulation of cholesterol metabolism by proteolysis by proteolysis of a membrane bound transcription factor. Cell 89, 331\u2013340 (1997).","journal-title":"Cell"},{"key":"BFng0401_375_CR6","first-page":"G1285","volume":"272","author":"M Muller","year":"1997","unstructured":"Muller, M. & Jansen, P.L. Molecular aspects of hepatobiliary transport. Am. J. Physiol. 272, G1285\u20131303 (1997).","journal-title":"Am. J. Physiol."},{"key":"BFng0401_375_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0092-8674(00)00097-0","volume":"103","author":"A Chawla","year":"2000","unstructured":"Chawla, A., Saez, E. & Evans, R.M. Don't know much bile-ology. Cell 103, 1\u20134 (2000).","journal-title":"Cell"},{"key":"BFng0401_375_CR8","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1002\/hep.510260641","volume":"26","author":"PJ Meier","year":"1997","unstructured":"Meier, P.J., Eckhardt, U., Schroeder, A., Hagenbuch, B. & Stieger, B. Substrate specificity of sinusoidal bile acid and organic anion uptake systems in rat and human liver. Hepatology 26, 1667\u20131677 (1997).","journal-title":"Hepatology"},{"key":"BFng0401_375_CR9","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/S0955-0674(98)80059-8","volume":"10","author":"B Stiewger","year":"1998","unstructured":"Stiewger, B. & Meier, P.J. Bile acid and xenobiotic transporters in liver. Curr. Opin. Cell. Biol. 10, 462\u2013467 (1998).","journal-title":"Curr. Opin. Cell. Biol."},{"key":"BFng0401_375_CR10","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1073\/pnas.95.1.282","volume":"95","author":"JM de Vree","year":"1998","unstructured":"de Vree, J.M. et al. Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis. Proc. Natl. Acad. Sci. USA 95, 282\u2013287 (1998).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFng0401_375_CR11","doi-asserted-by":"publisher","first-page":"D176","DOI":"10.2741\/A273","volume":"3","author":"JYL Chiang","year":"1997","unstructured":"Chiang, J.Y.L. Regulation of bile acid synthesis. Front. Biosci. 3, D176\u2013D193 (1997).","journal-title":"Front. Biosci."},{"key":"BFng0401_375_CR12","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1038\/383728a0","volume":"383","author":"BA Janowski","year":"1996","unstructured":"Janowski, B.A., Willy, P.J., Devi, T.R., Falck, J.R. & Mangelsdorf, D.J. An oxysterol signaling pathway mediated by the nuclear receptor LXRa. Nature 383, 728\u2013731 (1996).","journal-title":"Nature"},{"key":"BFng0401_375_CR13","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/S0092-8674(00)81432-4","volume":"93","author":"DJ Peet","year":"1998","unstructured":"Peet, D.J. et al. Cholesterol and bile acid metabolisms are impaired in mice lacking the nuclear oxysterol receptor LXR \u03b1. Cell 93, 693\u2013704 (1998).","journal-title":"Cell"},{"key":"BFng0401_375_CR14","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1126\/science.284.5418.1362","volume":"284","author":"M Makishima","year":"1999","unstructured":"Makishima, M. et al. Identification of a nuclear receptor for bile acids. Science 284, 1362\u20131365 (1999).","journal-title":"Science"},{"key":"BFng0401_375_CR15","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1126\/science.284.5418.1365","volume":"284","author":"DJ Parks","year":"1999","unstructured":"Parks, D.J. et al. Bile acids: natural ligands for an orphan nuclear receptor. Science 284, 1365\u20131368 (1999).","journal-title":"Science"},{"key":"BFng0401_375_CR16","doi-asserted-by":"publisher","first-page":"6660","DOI":"10.1073\/pnas.96.12.6660","volume":"96","author":"M Nitta","year":"1999","unstructured":"Nitta, M., Ku, S., Brown, C., Okamoto, A.Y. & Shan, B. CPF: an orphan nuclear receptor that regulates liver-specific expression of the human cholesterol 7a-hydroxylase gene. Proc. Natl. Acad. Sci. USA 96, 6660\u20136665 (1999).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFng0401_375_CR17","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/S1097-2765(00)00051-4","volume":"6","author":"B Goodwin","year":"2000","unstructured":"Goodwin, B. et al. A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol. Cell 6, 517\u2013526 (2000).","journal-title":"Mol. Cell"},{"key":"BFng0401_375_CR18","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/S1097-2765(00)00050-2","volume":"6","author":"TT Lu","year":"2000","unstructured":"Lu, T.T. et al. Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol. Cell 6, 507\u2013515 (2000).","journal-title":"Mol. Cell"},{"key":"BFng0401_375_CR19","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/S0092-8674(00)00062-3","volume":"102","author":"CJ Sinal","year":"2000","unstructured":"Sinal, C.J. et al. Targeted disruption of the nuclear receptor FXR\/BAR impairs bile acid and lipid homeostasis. Cell 102, 731\u2013744 (2000).","journal-title":"Cell"},{"key":"BFng0401_375_CR20","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1089\/dna.1993.12.283","volume":"12","author":"DR Powell","year":"1993","unstructured":"Powell, D.R. & Suwanichkul, A. HNF1 activates transcription of the human gene for insulin-like growth factor binding protein-1. DNA Cell Biol. 12, 283\u2013289 (1993).","journal-title":"DNA Cell Biol."},{"key":"BFng0401_375_CR21","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1016\/S0021-9258(17)42263-0","volume":"269","author":"MH Wong","year":"1994","unstructured":"Wong, M.H., Oelkers, P., Craddock, A.L. & Dawson, P.A. Expression cloning and characterization of the hamster ileal sodium-dependent bile acid transporter. J. Biol. Chem. 269, 1340\u20131347 (1994).","journal-title":"J. Biol. Chem."},{"key":"BFng0401_375_CR22","first-page":"G377","volume":"271","author":"DM Christie","year":"1996","unstructured":"Christie, D.M., Dawson, P.A., Thevananther, S. & Shneider, B.L. Comparative analysis of the ontogeny of a sodium-dependent bile acid transporter in rat kidney and ileum. Am. J. Physiol. 271, G377\u2013385 (1996).","journal-title":"Am. J. Physiol."},{"key":"BFng0401_375_CR23","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1172\/JCI117179","volume":"93","author":"S Ishibashi","year":"1994","unstructured":"Ishibashi, S., Goldstein, J.L., Brown, M.S., Herz, J. & Burns, D.K. Massive xanthomatosis and atherosclerosis in cholesterol-fed low density lipoprotein receptor-negative mice. J. Clin. Invest. 93, 1885\u20131893 (1994).","journal-title":"J. Clin. Invest."},{"key":"BFng0401_375_CR24","doi-asserted-by":"publisher","first-page":"3459","DOI":"10.1073\/pnas.75.7.3459","volume":"75","author":"TE Felker","year":"1978","unstructured":"Felker, T.E., Hamilton, R.L. & Havel, R.J. Secretion of lipoprotein-X by perfused livers of rats with cholestasis. Proc. Natl. Acad. Sci. USA 75, 3459\u20133463 (1978).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFng0401_375_CR25","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1172\/JCI108393","volume":"57","author":"E Manzato","year":"1976","unstructured":"Manzato, E. et al. Formation of lipoprotein-X. Its relationship to bile compounds. J. Clin. Invest. 57, 1248\u20131260 (1976).","journal-title":"J. Clin. Invest."},{"key":"BFng0401_375_CR26","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1172\/JCI106585","volume":"50","author":"KR Norum","year":"1971","unstructured":"Norum, K.R., Glomset, J.A., Nichols, A.V. & Forte, T. Plasma lipoproteins in familial lecithin: cholesterol acyltransferase deficiency: physical and chemical of low and high-density lipoproteins. J. Clin. Invest. 50, 1131\u20131140 (1971).","journal-title":"J. Clin. Invest."},{"key":"BFng0401_375_CR27","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S0022-2275(20)37233-3","volume":"38","author":"R van Antwerpen","year":"1997","unstructured":"van Antwerpen, R. et al. Cryo-electron microscopy of low-density lipoprotein and reconstituted discoidal high density lipoprotein: imaging of the apolipoprotein moiety. J. Lipid Res. 38, 659\u2013669 (1997).","journal-title":"J. Lipid Res."},{"key":"BFng0401_375_CR28","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1111\/j.1432-1033.1977.tb11654.x","volume":"77","author":"P Laggner","year":"1977","unstructured":"Laggner, P. et al. The lipid bilayer structure of the abnormal human plasma lipoprotein X. An X-ray small-angle-scattering study. Eur. J. Biochem. 77, 165\u2013171 (1977).","journal-title":"Eur. J. Biochem."},{"key":"BFng0401_375_CR29","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1097\/00041433-199606000-00010","volume":"7","author":"MA Austin","year":"1996","unstructured":"Austin, M.A. & Edwards, K.L. Small, dense low-density lipoproteins, the insulin resistance syndrome and noninsulin-dependent diabetes. Curr. Opin. Lipidol. 7, 167\u2013171 (1996).","journal-title":"Curr. Opin. Lipidol."},{"key":"BFng0401_375_CR30","doi-asserted-by":"publisher","first-page":"2974","DOI":"10.1074\/jbc.270.7.2974","volume":"270","author":"GE Homanics","year":"1995","unstructured":"Homanics, G.E. et al. Mild dyslipidemia in mice following targeted inactivation of the hepatic lipase gene. J. Biol. Chem. 270, 2974\u201380 (1995).","journal-title":"J. Biol. Chem."},{"key":"BFng0401_375_CR31","doi-asserted-by":"publisher","first-page":"36912","DOI":"10.1074\/jbc.274.52.36912","volume":"274","author":"B F\u00f6ger","year":"1999","unstructured":"F\u00f6ger, B. et al. Cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin cholesterol acyltransferase transgenic mice. J. Biol. Chem. 274, 36912\u201336920 (1999).","journal-title":"J. Biol. Chem."},{"key":"BFng0401_375_CR32","doi-asserted-by":"publisher","first-page":"2817","DOI":"10.1021\/bi00684a005","volume":"14","author":"RW Mahley","year":"1975","unstructured":"Mahley, R.W., Weisgraber, K.H., Innerarity, T., Brewer, H.B., Jr. & Assmann, G. Swine lipoproteins and atherosclerosis. Changes in the plasma lipoproteins and apoproteins induced by cholesterol feeding. Biochemistry 14, 2817\u20132823 (1975).","journal-title":"Biochemistry"},{"key":"BFng0401_375_CR33","doi-asserted-by":"crossref","first-page":"10448","DOI":"10.1016\/S0021-9258(18)82220-7","volume":"268","author":"A Stolz","year":"1993","unstructured":"Stolz, A. et al. cDNA cloning of the human hepatic bile acid-binding protein. A member of the monomeric reductase gene family. J. Biol. Chem. 268, 10448\u201310457 (1993).","journal-title":"J. Biol. Chem."},{"key":"BFng0401_375_CR34","doi-asserted-by":"publisher","first-page":"13209","DOI":"10.1073\/pnas.94.24.13209","volume":"94","author":"M Stoffel","year":"1997","unstructured":"Stoffel, M. & Duncan, S.A. The maturity-onset diabetes of the young (MODY1) transcription factor HNF4\u03b1 regulates expression of genes required for glucose transport and metabolism. Proc. Natl. Acad. Sci. USA 94, 13209\u201313214 (1997).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFng0401_375_CR35","first-page":"G810","volume":"261","author":"M Ananthanarayanan","year":"1991","unstructured":"Ananthanarayanan, M., Bucuvalas, J.C., Shneider, B.L., Sippel, C.J. & Suchy, F.J. An ontogenically regulated 48-kDa protein is a component of the Na(+)-bile acid cotransporter of rat liver. Am. J. Physiol. 261, G810\u2013817 (1991).","journal-title":"Am. J. Physiol."},{"key":"BFng0401_375_CR36","first-page":"G231","volume":"271","author":"AJ Bergwerk","year":"1996","unstructured":"Bergwerk, A.J. et al. Immunologic distribution of an organic anion transport protein in rat liver and kidney. Am. J. Physiol. 271, G231\u2013238 (1996).","journal-title":"Am. J. Physiol."},{"key":"BFng0401_375_CR37","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1101\/gad.5.6.1042","volume":"5","author":"DB Mendel","year":"1991","unstructured":"Mendel, D.B., Hansen, L.P., Graves, M.K., Conley, P.B. & Crabtree, G.R. HNF-1 \u03b1 and HNF-1 \u03b2 (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro. Genes Dev. 5, 1042\u20131056 (1991).","journal-title":"Genes Dev."},{"key":"BFng0401_375_CR38","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/S0022-2275(20)37923-2","volume":"24","author":"KDR Setchell","year":"1983","unstructured":"Setchell, K.D.R., Lawson, A.M., Tanida, N. & Sjovall, J. General methods for the analysis of metabolic profiles of bile acids and related compounds in feces. J. Lipid Res. 24, 1085\u20131100 (1983).","journal-title":"J. Lipid Res."},{"key":"BFng0401_375_CR39","doi-asserted-by":"publisher","first-page":"4169","DOI":"10.1021\/bi00013a004","volume":"34","author":"KDR Setchell","year":"1995","unstructured":"Setchell, K.D.R. et al. \u039422-Ursodeoxycholic acid, a unique metabolite of administered ursodeoxycholic acid in rats, indicating partial \u03b2-oxidation as a major pathway for bile acid metabolism. Biochemistry 34, 4169\u20134178 (1995).","journal-title":"Biochemistry"},{"key":"BFng0401_375_CR40","doi-asserted-by":"publisher","first-page":"1776","DOI":"10.1172\/JCI117163","volume":"93","author":"K Aalto-Setala","year":"1994","unstructured":"Aalto-Setala, K. et al. Intestinal expression of human apolipoprotein A-IV in transgenic mice fails to influence dietary lipid absorption or feeding behavior. J. Clin. Invest. 93, 1776\u20131786 (1994).","journal-title":"J. Clin. Invest."},{"key":"BFng0401_375_CR41","doi-asserted-by":"publisher","first-page":"10194","DOI":"10.1073\/pnas.95.17.10194","volume":"95","author":"E Sehayek","year":"1998","unstructured":"Sehayek, E. et al. Biliary cholesterol excretion: a novel mechanism that regulates dietary cholesterol absorption. Proc. Natl. Acad. Sci. USA 95, 10194\u201310199 (1998).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFng0401_375_CR42","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1093\/clinchem\/43.4.669","volume":"43","author":"DM Levine","year":"1997","unstructured":"Levine, D.M. & Williams, K.J. Automated measurements of mouse apolipoprotein B: convenient screening tool for mouse models of atherosclerosis. Clin. Chem. 43, 669\u2013674 (1997).","journal-title":"Clin. Chem."},{"key":"BFng0401_375_CR43","doi-asserted-by":"publisher","first-page":"31006","DOI":"10.1074\/jbc.272.49.31006","volume":"272","author":"BL Shneider","year":"1997","unstructured":"Shneider, B.L. et al. Cloning and characterization of a novel peptidase from rat and human ileum. J. Biol. Chem. 272, 31006\u201331015 (1997).","journal-title":"J. Biol. Chem."}],"container-title":["Nature Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/ng0401_375.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ng0401_375","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ng0401_375.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T20:27:00Z","timestamp":1684441620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ng0401_375"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,4]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2001,4]]}},"alternative-id":["BFng0401_375"],"URL":"https:\/\/doi.org\/10.1038\/86871","relation":{},"ISSN":["1061-4036","1546-1718"],"issn-type":[{"value":"1061-4036","type":"print"},{"value":"1546-1718","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,4]]}}}